Tumor microenvironment and immunometabolic reprogramming in pancreatic ductal adenocarcinoma: Barriers and breakthroughs in immunotherapy.

Clinically, it is a significant challenge to realize effective treatment of pancreatic ductal adenocarcinoma (PDAC), given its heavily immunosuppressive and heterogeneous tumor microenvironment (TME). Emerging evidence documented the pivotal function of immunometabolism in shaping the TME and driving PDAC progression. Tumor cells undergoing metabolic reprogramming, driven by heavily immunosuppressive and heterogeneous TME, can enable adaptation to a hypoxic environment. These metabolic alterations may further facilitate tumor survival and invasion, as well as compromising the function and phenotype of immune subsets. The resultant metabolic-immune interaction can subsequently induce immune evasion and promote tumor progression. Recent breakthroughs in immunotherapy have unveiled potential strategies to counteract the immunosuppressive TME and enhance patient prognoses. Accordingly, the present review intended to furnish a thorough and detailed overview of the current understanding of the immune microenvironment and metabolic regulation in PDAC. Furthermore, it explored key challenges in therapeutic translation and outlined opportunities for intervention. By investigating the complex relationship between immunological dysfunction and metabolic pathways, this study is anticipated to explore innovative strategies to reinforce the potential of immunotherapy, thereby offering effectiveness and personalization in therapeutic options for patients with PDAC.